Glucose Control in Critically Ill Patients With Severe Sepsis—Reply

In reply

As we stated in our review of nutrition support, it was also our recommendation based on current data that for critically ill patients receiving principally enteral nutrition, which is generally inadequate in the first 72 hours, a target goal of modest hyperglycemia of a glucose level less than 150 mg/dL (to convert to millimoles per liter, multiply by 0.0555) is appropriate for intensive insulin therapy.¹ This reflects the findings of the NICE-SUGAR study, which compared tight glucose control of 81 to 108 mg/dL with an intermediate level of less than 180 mg/dL and found a significantly higher risk of hypoglycemia in the intensive insulin therapy group but also an increased mortality.² In their initial landmark study, van den Berghe et al³ found that tight glucose control, treatment to true normoglycemia (glucose level 80-110 mg/dL), and early and aggressive feeding decreased hospital mortality by one-third in surgical intensive care unit patients, especially those with sepsis and multisystem organ failure and longer intensive care unit stays. There were a number of methodological differences between the original van den Berghe et al study³ and the NICE-SUGAR study including different target ranges for blood glucose level, different accuracies of glucometers, and varying levels of expertise of the participating institutions.⁴ Most importantly, as far as we can determine, all subsequent randomized trials after the initial van den Berghe et al study used enteral nutrition primarily. Furthermore, subsequent trials also had much tighter glucose regulation in the control group than in the original van den Berghe study in which the control group received insulin only when their blood glucose level exceeded 200 mg/dL, which was the standard therapy at the time. Thus, recent trials have been comparisons of very tight control with a high and sometimes unacceptable risk of hypoglycemia to less severe but still tight control to about the 150-mg/dL level with much less risk of hypoglycemia but still substantially better glucose control than in the pre–van den Berghe et al years. A second important consideration is that enteral nutrition may be an important factor in the development of hypoglycemia, first because intestinal absorption is often impaired in critically ill patients and second because tube feeding is often discontinued while insulin continues to be administered during intensive insulin therapy. Total parenteral nutrition is also associated with much higher insulin levels for the same amount of nutrient intake,⁵ implying insulin resistance, which may be partially protective to the development of insulin-induced hypoglycemia. Thus, for the much smaller group of critically ill patients, that is, those receiving principally total parenteral nutrition as both early and adequate feeding, a lower goal level of glucose may be warranted based on findings of the initial and unique van den Berghe study where tight control led to an improved outcome compared with both moderate control as well as loose control.² However, it would be a reasonable alternative to accept the less intense target value of less than 150 mg/dL for these individuals as well. Ultimately, the optimal target for blood glucose level in critically ill patients receiving total parenteral nutrition will need to be determined by additional study.